Lecture 7.2 - Blood Borne Viruses - HIV PDF

Global distribution of HIV: ◦The vast majority of people with HIV are in low and middle-income countries ◦In 2022, there were: ‣ 25.6 million people with HIV in the African region ‣ 3.8 million people with HIV in the Americas ‣ 3.9 million people with HIV in...

Global distribution of HIV: ◦The vast majority of people with HIV are in low and middle-income countries ◦In 2022, there were: ‣ 25.6 million people with HIV in the African region ‣ 3.8 million people with HIV in the Americas ‣ 3.9 million people with HIV in the South East Asian region ‣ 3.0 million people with HIV in the European region Prevalence of HIV in the UK: ◦An estimated 102,168 people were living with HIV in the UK in 2022 - includes undiagnosed cases ‣ Homosexual men - 46.9% ‣ Heterosexuals - 48.6% ‣ IV drug use - 1.8% ‣ Vertical transmission - 1.8% Human immunodeficiency virus (HIV): ◦Human immunodeficiency virus (HIV-1 and HIV-2) ◦Has its own reverse transcriptase to convert RNA into DNA ◦Retrovirus ("backwards") ‣ ssRNA, DNA, ssRNA ◦Infects cells with CD4 ◦Surface receptor: ‣ T-helper lymphocytes ‣ Monocytes/macrophages ◦HIV replicates inside cells -> spreads to/infects more cells Replication of HIV: Progression of CD4+ T lymphocyte count in HIV infection:  Progression of CD4+ T lymphocytes and viral load in HIV infection: HIV staging: Conditions associated with AIDS: Transmission: ◦Contact of infected bodily fluids with mucosal tissue/blood: ‣ Unprotected sexual intercourse (anal/vaginal) ‣ IV drug users (sharing needles) ◦Medical procedures: ‣ Blood/blood-products transfusion ‣ Surgery ‣ Needlestick injury ‣ Skin grafts, organ transplant ◦Vertical transmission: ‣ Mother to baby (during pregnancy, at the time of birth, breast milk) Factors affecting HIV transmission: ◦Type of exposure: ‣ Type of sexual act (use of condoms) ‣ Transfusion, needlestick, mucous membrane  ‣ Other STI (inflammation of genital tract) ‣ Sexual assault ◦Viral level (viral load) in blood ‣ U=U -> sustained undetectable viral load (VL) for 6/12 means that HIV is untransmittable Living with HIV in the UK: ◦Life expectancy and quality of life now excellent: ‣ Early detection treatment ‣ Adherence to treatment ‣ Healthy living -> smoking, alcohol, metabolic problems ◦Late detection = worse prognosis (x10 risk death in 1st year) ‣ 66% of over 65 year olds detected late Infections caused by HIV (weakened immune system): Diagnostic tests: ◦Blood test - serology: ‣ HIV antigen (Ag) - viral capsid protein p24 ‣ HIV antibody (Ab) - early antibodies to p24 and gp41 (transmembrane protein). Appear at 3-12 weeks and persist for life ‣ Current tests - detects both Ag and Ab ‣ Result on same day ‣ May get false negative result ◦Blood tests - PCR: ‣ Detects HIV nucleic acid ‣ Highly sensitive ‣ Detects very early infection (few days) ‣ Used for follow-up/treatment response ◦"Rapid" tests - low cost, < 1 hour  ‣ Usually detect HIV antibody ‣ Blood test (finger-prick) ‣ Oral (saliva) ‣ In-home tests ‣ Postal testing ‣ If negative - accurate ‣ May get false positive result -> need to confirm with serology Who should be tested?: ◦ Patients presenting with the following: ‣ Respiratory: bacterial pneumonia/TB ‣ Neurology: meningitis/dementia ‣ Dermatology: severe psoriasis Recurrent/multi-dermal shingles ‣ Gastroenterology: Chronic diarrhoea/weight loss ‣ Haematology: any unexplained blood abnormality ‣ Oncology: lymphoma, anal cancer ‣ Gynaecology: cervical intraepithelial neoplasia (CIN) ‣ Sexually transmitted diseases: Hep B/Hep C Aims of HIV therapy: ◦Undetectable HIV viral load ◦Reconstitute CD4 count/immune system ◦Reduce risk of transmission ◦Good quality of life (low side effects, compliance) ◦Normalise lifespan Targets for HIV therapy: ◦Post attachment inhibitors ◦Fusion inhibitors ◦Reverse transcriptase inhibitors ◦Integrase inhibitors ◦Protease inhibitors Which ART?:  Why give 3 or more ART?: ◦Millions of rounds of viral replication each day ◦Virus mutates (changes/adapts) every 2-3 rounds ◦Resistance to drugs can develop in days ◦1 drug - resistance develops quickly ◦3 drugs - harder to develop resistance ◦Patient must keep taking drugs Considerations for exposure to HIV: ◦Emergency anti-HIV medicine called post-exposure prophylaxis (PAP) may stop individuals becoming infected if started within 72 hours of possible exposure to the virus - it's recommended that they start it as soon as possible, ideally within 24 hours ◦An early diagnosis means treatment can start sooner, which can improve the chances of controlling the virus, reduce the risk of becoming more unwell and reduce the chance of passing the virus on to others ◦Both positive and negative HIV tests may need to be repeated 1 to 3 months after potential exposure to HIV infection (this is known as the window period) Strategies for prevention of HIV: ◦Education (understanding of spread/control, reduce stigma) ◦Increase condom usage ◦Prevention of mother-to-child transmission (testing) ◦Increase testing ◦Needle and syringe programme (IV drug users) ◦Male circumcision ◦Post-exposure prophylaxis (PEP) ◦Pre-exposure prophylaxis (PrEP) - for people who are at high risk of HIV infection, for example, those whose partner is HIV positive ◦Development of vaccine(s) The good news: ◦Decline in new diagnoses in homosexual men ◦Decline in new diagnoses in Black African heterosexuals in UK ◦Decline in new HIV diagnoses, AIDS and deaths ◦Reduction in time to start treatment Future therapies: ◦Use of haematopoietic stem cell transplantation (HSCT) ‣ Absence of surface expression of the CCR5 Ethical dilemmas in HIV: ◦Psychological impact of diagnosis ◦Dealing with stigma ◦Patient confidentiality vs: ‣ Health of mother ‣ Health of unborn child ‣ Health of sexual contact (husband)  ‣ Health of older child ‣ Risk to patients/staff at workplace